NDLI: The role of climate and out-of-Africa migration in the frequencies of risk alleles for 21 human diseases

Content Provider	Springer Nature : BioMed Central
Author	Blair, Lily M. Feldman, Marcus W.
Abstract	Background Demography and environmental adaptation can affect the global distribution of genetic variants and possibly the distribution of disease. Population heterozygosity of single nucleotide polymorphisms has been shown to decrease strongly with distance from Africa and this has been attributed to the effect of serial founding events during the migration of humans out of Africa. Additionally, population allele frequencies have been shown to change due to environmental adaptation. Here, we investigate the relationship of Out-of-Africa migration and climatic variables to the distribution of risk alleles for 21 diseases. Results For each disease, we computed the regression of average heterozygosity and average allele frequency of the risk alleles with distance from Africa and 9 environmental variables. We compared these regressions to a null distribution created by regressing statistics for SNPs not associated with disease on distance from Africa and these environmental variables. Additionally, we used Bayenv 2.0 to assess the signal of environmental adaptation associated with individual risk SNPs. For those SNPs in HGDP and HapMap that are risk alleles for type 2 diabetes, we cannot reject that their distribution is as expected from Out-of-Africa migration. However, the allelic statistics for many other diseases correlate more closely with environmental variables than would be expected from the serial founder effect and show signals of environmental adaptation. We report strong environmental interactions with several autoimmune diseases, and note a particularly strong interaction between asthma and summer humidity. Additionally, we identified several risk genes with strong environmental associations. Conclusions For most diseases, migration does not explain the distribution of risk alleles and the worldwide pattern of allele frequencies for some diseases may be better explained by environmental associations, which suggests that some selection has acted on these diseases.
Related Links	https://bmcgenomdata.biomedcentral.com/counter/pdf/10.1186/s12863-015-0239-3.pdf
Ending Page	12
Page Count	12
Starting Page	1
File Format	HTM / HTML
ISSN	27306844
DOI	10.1186/s12863-015-0239-3
Journal	BMC Genomic Data
Issue Number	1
Volume Number	16
Language	English
Publisher	BioMed Central
Publisher Date	2015-07-14
Access Restriction	Open
Subject Keyword	Life Sciences Animal Genetics and Genomics Microbial Genetics and Genomics Plant Genetics and Genomics Genetics and Population Dynamics Environmental adaptation Human disease risk loci Positive selection Genome-wide association studies Serial founder effect
Content Type	Text
Resource Type	Article
Subject	Health Informatics Genetics
Journal Impact Factor	1.9/2023
5-Year Journal Impact Factor	1.9/2023

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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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